We will establish a comprehensive Center to study the structural biology of HIV/Host interactions involved in viral trafficking and assembly. Our work will be focused in four areas: 1) Viral RNA and Gag Trafficking, 2) Virus Budding, 3) Virus Structure, and 4) Early Events and TRIMSa Restriction. Our studies are designed to define the molecular basis for Rev-dependent nuclear export, reveal the structures of host/virus complexes and enzymes that facilitate virus budding, and reconstruct the immature and mature HIV-1 virions in unprecedented detail. Collaborative interactions will extend our research to include structural studies of TRIMSa restriction, the infectivity enhancement of HIV-1 Nef, and a series of host factors involved in the early stages of viral replication. We will also develop and apply new computational and experimental methods for analyzing host/virus complexes, imaging how they traffic in the cell, studying how they function as molecular machines, and inhibiting their functions. This work will lay the groundwork for new antiviral strategies and will also help develop HIV into an unparalleled model system for studying how a human virus interacts with its cellular host.